Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study.

Purpose: Adrenal androgens activate the androgen receptor and stimulate prostate cancer growth. Ketoconazole is used as an inhibitor of adrenal androgen synthesis in men with androgen-independent prostate cancer. This study analyzes the relationship between pretreatment androgen levels and outcome following ketoconazole treatment.

Pharmacokinetic modulation of oral etoposide by ketoconazole in patients with advanced cancer.

Purpose: Etoposide is a widely used cytotoxic drug that is commercially available in both intravenous and oral formulations. High interpatient pharmacokinetic variability has been associated with oral etoposide administration. Various strategies used in the past to reduce such variability have not been successful.

Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors.

Purpose: To investigate the role of high-dose chemotherapy (HDCT) as first-line treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic clinical features. Serum tumor marker decline during chemotherapy was assessed prospectively as a predictor of treatment outcome.

Patients And Methods: In this randomized phase III trial, previously untreated patients with intermediate- or poor-risk GCT received either four cycles of standard bleomycin, etoposide, and cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT).

The impact of prior radical prostatectomy in men with metastatic castration recurrent prostate cancer: a pooled analysis of 9 Cancer and Leukemia Group B Trials.

Purpose: A prior report suggested that radical prostatectomy may confer a survival advantage to patients with metastatic castration recurrent prostate cancer. Therefore, a pooled analysis of 9 trials performed by Cancer and Leukemia Group B was done to determine if men with metastatic castration recurrent prostate cancer who underwent prior prostatectomy had improved clinical outcomes, such as overall, prostate specific, progression-free and PSA progression-free survival, than men who did not undergo prior prostatectomy.

Materials And Methods: Data from 9 multi-institutional trials performed by Cancer and Leukemia Group B were combined.

Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma.

Purpose: Conventional chemotherapy for urothelial carcinoma, such as methotrexate, vinblastine, doxorubicin and cisplatin, is associated with significant toxicity. We have previously reported a low toxicity and yet moderately active regimen containing weekly infusional cisplatin and high dose 5-fluorouracil/leucovorin for advanced urothelial carcinoma. We tested the efficacy and toxicity of adding paclitaxel to that regimen.

Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in patients with locally advanced bladder cancer.

Background: Despite the general acceptance of gemcitabine/cisplatin in metastatic bladder cancer, its role and tolerability in the adjuvant setting, in which renal insufficiency is common, is unclear.

Patients And Methods: A total of 39 patients with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2) were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical cystectomy. All toxicities were evaluated by the National Cancer Institute Common Toxicity Criteria.

Monitoring response, prediction methodology, staging, and imaging in prostate cancer.

The predictive values of various tests and examinations are assessed as they relate to prostate cancer progression and treatment. The usefulness of post-treatment biopsy specimens is greatest 2 years after radiation therapy completion. Gleason grading is not reliable in the setting of hormonal ablation therapy.

Clinical outcomes by age in men with hormone refractory prostate cancer: a pooled analysis of 8 Cancer and Leukemia Group B (CALGB) studies.

Purpose: We determined if age is a prognostic factor of clinical outcomes, specifically overall survival, disease-free survival and progression-free survival in men with hormone refractory prostate cancer.

Materials And Methods: Data from 8 multi-institutional trials performed by Cancer and Leukemia Group B were combined. Eligible patients had progressive adenocarcinoma of the prostate after androgen ablation, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate hematological, renal and hepatic function.

Activities and accomplishments of the cancer and leukemia group B genitourinary committee.

The Cancer and Leukemia Group B Genitourinary (GU) Committee has developed a multidisciplinary approach to treatment of GU cancer and has integrated correlative science research into the major research themes of the GU Committee. In localized prostate cancer, trials have evaluated novel approaches in radiation therapy. For patients with recurrence after local therapy, a trial evaluating local recurrence with salvage prostatectomy and a study of systemic therapy with "peripheral androgen blockade" were undertaken.

Prognostic significance of plasma scatter factor/hepatocyte growth factor levels in patients with metastatic hormone- refractory prostate cancer: results from cancer and leukemia group B 150005/9480.

Background: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a polypeptide growth factor thought to be important in the growth and spread of prostatic carcinoma.

Patients And Methods: Scatter factor/HGF levels in pretreatment plasma samples from 171 men with metastatic hormone-refractory prostate cancer enrolled in CALGB 9480 were quantified by solid-phase, enzyme-linked immunosorbent assay.

Results: The Cox proportional hazards model was used to assess the prognostic importance of SF/HGF with adjustment for established prognostic factors.

Classification of renal neoplasms based on molecular signatures.

Purpose: Gene expression microarray studies have demonstrated distinct molecular signatures for different types of renal neoplasms based on overall gene expression patterns. However, in most of these studies the investigators used renal tumors with defined histology. We analyzed a test set of renal tumors in double-blind fashion using recently established molecular profiles of renal tumors as benchmarks.

Variability in mesothelioma tumor response classification.

Objective: The objective of our study was to evaluate observer variability in the measurement of temporal change in mesothelioma tumor thickness and in the resulting tumor response classification from CT scans. In addition, the performance of a semiautomated measurement method was evaluated.

Materials And Methods: Four observers individually used an interface that displayed two serial CT scans from the same patient to measure mesothelioma tumor thickness on the follow-up CT scans of 22 patients based on baseline scan measurements.

Ranpirnase--an antitumour ribonuclease: its potential role in malignant mesothelioma.

Ranpirnase (Onconase) is a novel cytotoxic ribonuclease. In clinical development as a single agent in patients with malignant mesothelioma (MM), at 480 microg/m2 intravenously weekly, analysis of survival indicated prolonged periods of stable disease in Phase II trials and a potential survival benefit, compared with doxorubicin, in a small unpublished Phase III trial. In all clinical studies it has generally demonstrated a favourable safety profile except for easily controlled allergic reactions and dose modifications for renal impairment.

A randomized phase II trial of the matrix metalloproteinase inhibitor BMS-275291 in hormone-refractory prostate cancer patients with bone metastases.

Background: BMS-275291 is a selective matrix metalloproteinase inhibitor (MMPI) that does not inhibit sheddases implicated in the dose-limiting arthritis of older MMPIs. We conducted a randomized phase II trial of two doses of BMS-275291 (1,200 versus 2,400 mg) in hormone-refractory prostate cancer (HRPC) patients with bone metastases to probe for a dose-response relationship and to assess differential toxicities. Serial serum and urine specimens were collected to assess for markers of bone metabolism.

A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma.

Purpose: Bryostatin-1 is a PKC modulator with direct anti-tumor activity and immunomodulatory properties. We combined different doses of Bryostatin-1 with IL-2 to determine effects on clinical response rate and T cell phenotype in patients with advanced kidney cancer.

Experimental Design: IL-2 naïve patients were given 11 x 10(6) IU subcutaneously of IL-2 on days 1-4, 8-11, and 15-18 of every 28-day cycle.

Weekly cisplatin plus infusional high-dose 5-fluorouracil and leucovorin (P-HDFL) for metastatic urothelial carcinoma: an effective regimen with low toxicity.

Background: Conventional systemic chemotherapy for metastatic urothelial carcinoma (UC) such as methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) or cisplatin, methotrexate, and vinblastine (CMV) is associated with significant dose-limiting toxicities and even treatment-related death. The authors developed a regimen that was designed to maintain efficacy, while reducing toxicities.

Methods: Between January 1998 and July 2003, 35 patients (median age, 71 yrs) with metastatic UC were treated with 4-week cycles of P-HDFL (cisplatin 35 mg/m(2), high-dose 5-fluorouracil [5-FU] 2,600 mg/m(2), and leucovorin 300 mg/m(2), on Days 1 and 8, all given by 24-hr infusion).

Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study.

Purpose: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients.

Material And Methods: Data from Cancer and Leukemia Group B study 9663 were reviewed.

Standard therapy for the treatment of malignant pleural mesothelioma.

Almost all of the established cytotoxic agents have now been examined both as single-agents and in combination chemotherapy regimens as treatment approaches for malignant pleural mesothelioma (MPM). Until recently, only few agents have consistently produced objective response rates greater than 20%, and no agent has improved median survival beyond 10 months. The recent development of several new cytotoxic agents, such as the novel antimetabolite pemetrexed, has yielded encouraging results.

Evaluation of semiautomated measurements of mesothelioma tumor thickness on CT scans.

Rationale And Objectives: To evaluate the clinical acceptability of semiautomated methods for the measurement of mesothelioma tumor thickness in computed tomography (CT) scans.

Materials And Methods: A computer interface was developed to allow the acquisition of semiautomated mesothelioma tumor thickness measurements, which require the manual selection of a point along the outer margin of the tumor in a CT section. After application of an automated lung segmentation method, the computer automatically identifies a corresponding point along the inner margin of the tumor (as represented by the lung boundary), constructs a line segment between the manually selected outer tumor margin point and the computer-determined inner tumor margin point, and computes tumor thickness as the length of this line segment.

Novel agents for the treatment of advanced kidney cancer.

Advanced kidney cancer accounts for over 12,000 deaths in the United States each year. Immunotherapy, typically interleukin-2 or interferon-alpha, have been the mainstay of treatment. Response rates are low for these immune-based treatments, and most patients with advanced kidney cancer succumb to their disease.

A phase II study of nilutamide in men with prostate cancer after the failure of flutamide or bicalutamide therapy.

Objective: To determine the prostate-specific antigen (PSA) response and time to PSA or radiographic progression in men with prostate cancer refractory to bicalutamide and/or flutamide therapy.

Patients And Methods: Men with histologically confirmed prostate cancer not amenable to curative surgery or radiation therapy were eligible for the study if they had radiographic or PSA progression on at least one antiandrogen (not nilutamide) despite continued androgen suppression and standard antiandrogen withdrawal periods. All men received nilutamide 150 mg/day orally for > or = 8 weeks unless there was unacceptable toxicity or disease progression.

Promising systemic therapy for renal cell carcinoma.

In the United States, advanced kidney cancer accounts for over 12,000 deaths each year. Immunotherapy with either interferon or interleukin-2 (IL-2) has been the standard of care for over two decades. High-dose IL-2 can apparently cure 10% to 15% of patients treated, but due to the required inpatient care and the attendant toxicities, it is only administered to less than 1,000 patients per year in the United States (Chiron, personal communication).